The olfactory receptors are the largest known family of genes, comprising one percent of the mammalian genome. These receptors determine the neural code used to carry olfactory information. Mutations in these genes are thought to underlie specific human anosmias. By determining the function of these receptors, we can better understand neural signal processing and certain olfactory deficits-information which may contribute to improvements in mental and olfactory capacities and the quality of human life. The goal of this project is to describe the odorant selectivity and functional domains of olfactory recpetors. These functional studies have been difficult because, as we have recently shown, olfactory receptors in heterologous cells fail to exit the endoplasmic reticulum and traffic to the plasma membrane. Our results suggest that olfactory receptors require accessory proteins for proper trafficking, and that these proteins may be specific to olfactory receptor neurons. We therefore propose to identify proteins that interact with the hydrophilic cytoplasmic domains of olfactory receptors and investigate whether these accessory proteins alter the trafficking and function of olfactory receptors. We also propose to use a novel cell line that expresses markers of olfactory receptor neurons to investigate olfactory receptor trafficking, desensitization, and domains within olfactory receptors that determine odorant selectivity.